Normal human peripheral blood mononuclear cells (PBMC) incubated with particulate staphylococci in short-term culture produce a potent inhibitor of neutrophil chemotaxis. We will examine the conditions of production and the mode of action of this inhibitor in order to understand better the modulation of human neutrophil chemotaxis by mononuclear cells in staphylococcal infections. The PBMC concentration and staphylococci/PBMC ratio necessary for optimal production of the inhibitor will be determined and the time course of the inhibitor production will be delineated. The role of monocytes, B cells and T cells in the production of the inhibitor will examined. Purified or partially purified inhibitor will be prepared and the mode of action of the inhibitor will be studied. After normal PBMC production of the inhibitor has been defined, PBMC and neutrophils from patients with recurrent staphylococcal soft-tissue infections will be studied. Twenty-five patients with recurrent staphylococcal disease will be recruited and studied longitudinally. The patients' clinical status will be objectively graded over several months. Their PBMC will be examined for abnormalities in inhibitor production and their neutrophils will be studied for abnormal sensitivity to the inhibitor. We will attept to correlate the patients' clinical course with changes in the production of or sensitivity to the inhibitor. In so doing, we will broaden our understanding of the interactions of bacteria, mononuclear cells and neutrophils. We may thus gain new insights into the causes of recurrent staphylococcal infections.